Our aim is to develop a simple and effective method for the delivery of rabies vaccines by topical application of adenovirus-based expression vectors using a skin patch in a noninvasive mode. The hypothesis is that the expression of rabies glycoprotein (GP) in the outer layer of skin can induce a systemic immune response against the virus. We have demonstrated that an immune response against a number of antigens could be elicited in both mice and macaques by noninvasive vaccination onto the skin (NIVS). These studies will further develop skin-targeted noninvasive vaccines, and specifically determine whether this novel approach for the delivery of vaccines can mobilize the immune repertoire toward a beneficial immune protection against rabies. In this project, the potential for skin-targeted noninvasive vaccines to elicit a protective immune response against rabies will be subjected to further investigation. A new generation of adenovirus vectors as novel vaccine carriers will be developed. Efficacy of NIVS will be compared to those induced by other means. The safety of NIVS will be studied by determining the fate of antigen DNA. The overall goal of these experiments is to determine whether rabies vaccines can be effectively and safely delivered by a skin patch that requires a lower level of skill in a needle-free manner. PROPOSED COMMERCIAL APPLICATION: Noninvasive vaccination onto the skin may boost vaccine coverages against rabies because the procedure is simple, effective, painless, and potentially safe. The development of a rabies vaccine patch may also make vaccination programs less dependent upon medical resources.